Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001577384 | SCV001804746 | uncertain significance | not provided | 2021-02-25 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV001866073 | SCV002185273 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2025-01-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg270*) in the HCN1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in HCN1 cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HCN1-related conditions. This premature translational stop signal has been observed in at least one individual who was not affected with HCN1-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 1208904). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002421213 | SCV002677633 | uncertain significance | Inborn genetic diseases | 2017-10-09 | criteria provided, single submitter | clinical testing | The p.R270* variant (also known as c.808C>T), located in coding exon 2 of the HCN1 gene, results from a C to T substitution at nucleotide position 808. This changes the amino acid from an arginine to a stop codon within coding exon 2. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of HCN1 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Department of Neurology, |
RCV001843425 | SCV002102575 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 10 | 2021-12-01 | no assertion criteria provided | clinical testing |